Investigation of the aetiology of Behçet's disease (BD) has focused predominantly on herpes simplex virus immunopathology, autoimmunity to oral mucosa or cross-reactive microbial antigens, and streptococcal infection. These aetiological factors might have a common denominator in microbial heat shock protein (HSP) which shows significant homology with the human mitochondrial HSP. Indeed, the uncommon serotypes of Streptococcus sanguis found in BD cross-react with the 65 kD HSP which also shares antigenicity with an oral mucosal antigen. T cell epitope mapping has identified 4 peptides derived from the sequence of the 65 kD HSP which stimulate specifically TCR gamma delta + lymphocytes from patients with BD. These peptides (111-125, 154-172, 219-233 and 311-325) show significant homology with the corresponding peptides derived from the human 60 kD HSP. The specific proliferative response of TCR gamma delta + lymphocytes elicited by the 4 peptides can be used as a laboratory test for the diagnosis of BD. The pathogenic significance of these peptides has been established by inducing uveitis in rats.